Age-related macular degeneration (AMD) is the leading cause of blindness in people 50 years of age or older in the developed world. The most prominent clinical and histological damage involves retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris;but it is the degeneration, dysfunction, and death of photoreceptors that accounts for the vision loss. Anatomical and functional studies have found that photoreceptor degeneration and loss occur before disease in the RPE/Bruch's membrane complex progresses to late AMD. Although the cone photoreceptor degeneration is secondary to rod death, it is the cone loss that causes major visual handicap. As such detecting early cone degeneration in a clinical setting is strategically critical to prevent vision loss. Cone inner segments become widened and misshapen during the degeneration;we hypothesize that enlargement and deformation of the parafoveal cones could be used as an early clinical sign for the diagnosis of AMD. Identifying these signs may be facilitated by high-resolution and high-fidelity retinal imaging. The cellular scale retinal image in the living human eye can only be achieved by adaptive optics (AO) assisted ophthalmoscopy. But current AO retinal imaging is hampered by insufficient image acquisition speed and inadequate image fidelity. In this application, we will develop a high- speed, high-resolution AO parallel confocal scanning ophthalmoscope (AO-PCSO) to facilitate diagnosis of AMD at an earlier stage. The instrument developed in this application is 'real-world'patient oriented. The AO-PCSO exceeds current AO retinal imaging modalities with significantly improved data collection efficiency and image fidelity. This application breaks the barrier to the study of AMD, seeking to shift current clinical practice paradigms from macro-scale to micro-scale by providing cellular diagnosis of retinal degenerative disease. The success of this research will significantly improve our ability to diagnose AMD at its onset and our knowledge of disease progression. High-speed image acquisition is a signature advance in confocal retinal imaging;it is not only important for imaging the elderly subjects but also equally important for studies involving children with early onset retinal disease. PUBLIC HEALTH RELEVANCE: Age-related macular degeneration (AMD) is the leading cause of blindness in people 50 years of age or older in the developed world. We will develop a high-speed, high-resolution retinal imager called adaptive optics parallel confocal scanning ophthalmoscope (AO-PCSO) to facilitate diagnosis of AMD at an earlier stage.